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ASPP2 maintains the integrity of mechanically stressed pseudostratified epithelia during morphogenesis

Author

Listed:
  • Christophe Royer

    (University of Oxford)

  • Elizabeth Sandham

    (University of Oxford)

  • Elizabeth Slee

    (University of Oxford)

  • Falk Schneider

    (University of Oxford
    University of Southern California)

  • Christoffer B. Lagerholm

    (University of Oxford)

  • Jonathan Godwin

    (University of Oxford
    University of Oxford)

  • Nisha Veits

    (University of Oxford)

  • Holly Hathrell

    (University of Oxford)

  • Felix Zhou

    (University of Oxford)

  • Karolis Leonavicius

    (University of Oxford
    Vilnius University)

  • Jemma Garratt

    (University of Oxford
    University of Oxford, Level 3, Women’s Centre, John Radcliffe Hospital)

  • Tanaya Narendra

    (University of Oxford
    University of Oxford, Level 3, Women’s Centre, John Radcliffe Hospital)

  • Anna Vincent

    (Oxford Business Park North)

  • Celine Jones

    (University of Oxford, Level 3, Women’s Centre, John Radcliffe Hospital)

  • Tim Child

    (University of Oxford, Level 3, Women’s Centre, John Radcliffe Hospital
    Oxford Business Park North)

  • Kevin Coward

    (University of Oxford, Level 3, Women’s Centre, John Radcliffe Hospital)

  • Chris Graham

    (University of Oxford, Level 3, Women’s Centre, John Radcliffe Hospital)

  • Marco Fritzsche

    (University of Oxford
    Rosalind Franklin Institute)

  • Xin Lu

    (University of Oxford)

  • Shankar Srinivas

    (University of Oxford)

Abstract

During development, pseudostratified epithelia undergo large scale morphogenetic events associated with increased mechanical stress. Using a variety of genetic and imaging approaches, we uncover that in the mouse E6.5 epiblast, where apical tension is highest, ASPP2 safeguards tissue integrity. It achieves this by preventing the most apical daughter cells from delaminating apically following division events. In this context, ASPP2 maintains the integrity and organisation of the filamentous actin cytoskeleton at apical junctions. ASPP2 is also essential during gastrulation in the primitive streak, in somites and in the head fold region, suggesting that it is required across a wide range of pseudostratified epithelia during morphogenetic events that are accompanied by intense tissue remodelling. Finally, our study also suggests that the interaction between ASPP2 and PP1 is essential to the tumour suppressor function of ASPP2, which may be particularly relevant in the context of tissues that are subject to increased mechanical stress.

Suggested Citation

  • Christophe Royer & Elizabeth Sandham & Elizabeth Slee & Falk Schneider & Christoffer B. Lagerholm & Jonathan Godwin & Nisha Veits & Holly Hathrell & Felix Zhou & Karolis Leonavicius & Jemma Garratt & , 2022. "ASPP2 maintains the integrity of mechanically stressed pseudostratified epithelia during morphogenesis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28590-4
    DOI: 10.1038/s41467-022-28590-4
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    References listed on IDEAS

    as
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